1. Field of the Invention
The present invention relates to a novel industrial process for the production of the antibiotic Phosphonomycin.
Phosphonomycin is L-(cis)-1,2-epoxypropyl-phosphonic acid and has the following structure (I): ##STR1## Phosphonomycin is a new antibiotic which was discovered in Spain in 1966. It was found for the first time in a fermentation broth of a strain of Streptomyces fradiae, isolated in the province of Alicante. Later there were found other strains of S. Virichromogenes and of S. Wedmorensis which also produced phosphomycin [Science, 166, 122-3, (1967)].
2. Prior Art
The biological and chemico-physical characteristics of (I) have been described by E. J. Glamkowski et al in J. Org. Chem., 35, 3510 (1970):
"Its bactericidal mode of action is via irreversible binding to the enzyme pyruvate-uridine diphospho-N-acetylglucosamine, thereby inhibiting cell wall synthesis. PA1 Phosphonomycin has been shown to be (-)-(1R,2S)-1,2-epoxypropylphosphonic acid. Proof of structure was obtained by synthesis together with a chemical determination of the absolute configuration."
Phosphonomycin has been prepared also synthetically (G. B. Christensen et al, Science, loc. Cit.; E. J. Glamkowski, J. Org. Chem., loc. cit.)
Essentially, this method of synthesis previously reported in the literature takes place through the following steps:
(1) Preparation of the t-butyl-phosphochlor idite or phosphochloridite, t-(BuO).sub.2 PCl; PA0 (2) Reaction of the latter with propargyl alcohol to obtain the t-butyl-propynyl-phosphite; PA0 (3) Isomerisation of the latter to the (allenic) propadienylphosphonate; PA0 (4) Hydrogenating same to the cis-propenylphosphonate; PA0 (5) Hydrolysis to obtain the cis-propenylphosphonic acid; PA0 (6) Epoxidation and optical resolution to obtain the L isomer of the desired phosphonomycin.